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You are watching: What is the role of lamellated granules in the stratum granulosum

StatPearls . Sweetheart Island (FL): StatPearls Publishing; 2021 Jan-.


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Introduction

The epidermis is comprised of 4 or 5 layers, depending on the location of the skin sampled.  these layers native deep to superficial room stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and also stratum corneum.  The stratum lucidum is typically only current in the thick skin uncovered in locations such as the palm or soles.  The basal layer of the epidermis consists of keratinocytes in their the very least differentiated form wherein they experience mitosis and proliferate.  together the keratinocytes mature and differentiate they migrate superficially, create keratin, and also eventually lose their nuclei and other moving organelles; the last cells type stratum corneum or the horny great of the skin. Keratin, the simple constituent protein the the skin and its appendages, is arranged in the kind of keratin filament bundles. Filaggrin is one of the major intermediate filament-associated protein that connect with keratin filaments in the skin. Its precursor type called profilaggrin accumulates in cytoplasmic granules of the granular layer in the kind of structures referred to as keratohyalin granules (KHG).

Keratohyalin granules generally exist within the stratum granulosum, through some current in the stratum spinosum. These granules are insoluble in water and also located within the cytoplasm wherein they encourage dehydration of the cell.  their chief duty seems to it is in cross-linking that keratin filaments which create the tight obstacle that is the epidermis, giving the body v an impermeable layer that protects from intrusion by international particles.  This process of cornification that the epidermis effected through KHG is well-known as keratinization.


Issues of Concern

This short article examines the histology of KHG discovered within the epidermal great of the skin and also will discuss the following: The structure and also functions that KHG, organization preparation prior to examination the granules, histochemistry and cytochemistry, electron microscopy, and relevant pathophysiology with clinical correlation. 


Structure

Skin & Mucosa

Keratohyalin granules are frequently present in the stratum granulosum of the epidermal layer of the skin (and epithelium the the mucosae). KHG room protein structures found in the keratinocytes the the stratum granulosum that appear in two main variants.  Globular KHG are uncovered in quickly separating epithelia, such together the dental mucosa; whereas, stellate KHG room in the slowly dividing normal epidermis.<1>  The granules frequently contain a mixture that keratin filament bundles, as well as the filament-associated protein loricrin, filaggrin, and also trichohyalin.<2><3>

Thymus

Additionally, KHG is additionally present in the cytoplasm of Hassall’s corpuscles the the thymus gland.<4> Hassall"s corpuscles, additionally called type VI epithelioreticular cell are current in the medulla that the thymus gland. Except the existence of KHG, their cytoplasm likewise contains intermediated fibers and may be keratinized. Although the an exact function of thymic KHG and also keratinization of Hassall"s corpuscles remains unknown, lock have been suggested to create IL-4 and also IL-7 to help with T lymphocyte development. 


Function

Keratinisation

Keratohyalin granules encourage the development of the epidermal cornified cabinet envelope, also known as cornification or keratinization.  Visualization of this granules in the assorted epidermal layers reflects that they flourish in size progressively as they relocate from the stratum spinosum towards the stratum corneum.<5>  In the smaller sized keratohyalin granules located within the deeper epidermal layers, dense aggregates the ribosomes can be checked out at the website of blebs, indicating protein assembly and initial keratin intermediary filament formation.<6>  together keratinocytes differentiate and the granules broaden in size, the keratohyalin granules convert keratin tonofilaments into a homogenous keratin matrix, vital step in cornification.<7>

The surname filaggrin is a contraction of ‘filament aggregating protein.’ In vitro experiments have presented that filaggrin causes bundling and also condensation of keratin intermediate filaments.<8> various techniques consisting of immunohistochemistry, immuno-electron microscopy, and also biochemical studies have revealed that profilaggrin, the large (>400 kDa) precursor protein that filaggrin, is the main constituent of the KHG.<9> In fact, the diversity of profilaggrin/filaggrin as constituents of the KHG renders these granules visible enabling demarcation of stratum granulosum by low-power light microscopy in skin sections stained with hematoxylin & eosin.<10>

The process of keratinization, i.e., the formation of the cornified cabinet envelope is a complex phenomenon. It requires cross-linking of miscellaneous proteins in the cabinet periphery, especially loricrin and involucrin at the shift zone in in between stratum granulosum and stratum corneum.<11> Profilaggrin is inactive in ~ the KHG, yet during epidermal differentiation of granular great keratinocytes committing to form the squames the stratum corneum, this granules vanish together profilaggrin rapidly processes into cost-free filaggrin monomers.<9> This process leads to condensation the the cytoskeleton and also flattening the the terminally separating granular cells right into corneal squames. A facility cascade the phosphatases and also proteases is connected in this quick degranulation event.<9>

Epidermal Moisturisation via water retention in stratum corneum

Within the squames, filaggrin undergoes more chemical change and proteolytic processing. Eventually, it division down completely to become natural moisturizing variable (NMF), a natural humectant in ~ the residual cytoplasmic an are of the squames structurally/chemically created of hygroscopic amino acids and also their derivatives.<10>

Other indirect functions

Through their contribution to keratinization and also water retention in stratum corneum, KHG and its ingredient proteins add to other attributes such as  UV protection, and also modulation the stratum corneum pH (to do it hostile for pathogenic microbes). Thus, as a whole, KHG, filaggrin, and related proteins are critical for common healthy function the the skin obstacle layers.


Tissue Preparation

Traditionally, acetic acid has actually been offered to obtain sheet preparations of the stratum granulosum from the epidermis and oral epithelium that rodents and man.<12> Contemporarily, a variety of effective methods of organization preparation because that the visualization of KHG have to be proposed.  traditional lab methods are typically suitable for preparation and also fixation of epidermal tissue. Reconstructed human being epidermis (RHE) provides a recently developed model to research epidermal to move kinetics including the KHG, lamellar bodies, and also other useful structures.  

Standard Method

A standard technique that was found to be effective is as follows.  Specimens need to be automatically processed complying with surgical excision and also washed once in 1X phosphate buffered solution.  small pieces room typically finest for preparation, frequently sizes less than 1 mm.  Tissue deserve to then it is in frozen in optimal cutting temperature medium for cryosection formation, or they have the right to be fixed in formaldehyde or ethanol before paraffin embedding, after i m sorry they room sliced and also placed on slides for more staining or analysis.<13><14>

Reconstructed person epidermis

Models of RHE have are advantageous for the evaluation of physio-chemical properties of the epidermis,  metabolic researches of pharmaceutical products, epidermal responses come irritants and also sensitizers, and assessment that cutaneous irritancy or phototoxicity.<15> RHE all set by culturing normal human keratinocytes at high cell thickness for few weeks (average - 14 days) in a serum-free and also high calcium (1.5 mM) tool on one inert polycarbonate filter at the air-liquid user interface showed histological features comparable to those it was observed in vivo in the epidermis: a proliferating basal layer and differentiating spinous, granular, and also cornified layers. Electron microscopy illustrated lamellar bodies, junctions, and keratohyalin granules.<15> together models room customizable because that studies including epidermal keratinocytes and also its key constituents such as KHG, lamellar bodies, keratin intermediate filaments, etc.


Histochemistry and Cytochemistry

A selection of histochemical and also immunohistochemical staining methods deserve to be supplied to examine KHG in organization samples.  Several instances are noted below, which at the time of their corresponding publications, noted greater understanding into the framework and duty of keratohyalin granules.

Hematoxylin and eosin (H & E) staining is a specifically effective an approach for examining KHG.  This is in huge part due to the hematoxylin stainability that the granules.  The stainability the KHG is thought to be as result of the fibrinogen gamma-chain protein uncovered within the granules, i m sorry is demonstrably basophilic.<16> The basophilic staining that KHG makes them show up blue on H & E staining, i beg your pardon facilitates to know of stratum granulosum in the epidermis native an H & E stained ar (Figure 1>.

Bennett’s reagent is a straightforward and rapid technique of identifying totally free sulfhydryl groups.<17>  The high number of cost-free sulfhydryl teams within KHG additionally makes histochemical staining with Bennett’s reagent possible.  Staining shows increased thickness of sulfhydryl teams within the stratum granulosum, v moderate staining in the stratum spinosum.<18>

The protein filaggrin, discovered within KHG, has actually a fairly high existence of histidine. Antibodies raised versus this protein have been offered to immunohistochemically visualize keratohyalin granules.<19>


Microscopy Electron

Electron microscopy has been displayed to be an effective technique in visualizing the process of cornification in the person skin, in which KHG beat a huge role.  Keratohyalin granules are evident as electron-dense granules that appear in the cytoplasm that cells whereby they can be seen forming a sheath roughly the tonofibrils and also ultimately associating with keratin filaments in the more superficial class of the epidermis.<20>  better insight right into the role of KHG in the cornification procedure initially involved light after treatment v proteases and also under visualization by electron microscopy. The result were that the thickening the the cabinet membranes in the stratum corneum is no the result of the enhancement of product from the exterior of the cell, but instead the deposition the protein material on the cytoplasmic side of the membrane.<21>


Pathophysiology

Unique attributes of keratohyalin granule immunohistochemistry have been supplied to evaluate numerous pathologic conditions of the skin and also have caused a much better understanding of healthy and balanced physiology as well.  Histochemistry that the granules in person oral leukoplakia produced staining through Pauly’s reagent, Congo red, and also hematoxylin, saying a high lot of protein within the granules; however, the keratohyalin granules did no react with Feulgen reagent, demonstrating the lack of DNA.<14>


Clinical Significance

The antiperinuclear variable is a rheumatoid arthritis-specific autoantibody the is present in 49-91% the patients with rheumatoid arthritis.  Immunohistochemical staining through antibodies directed versus antiperinuclear element shows staining of KHG.<22>

Identification the hypergranulosis or hypogranulosis ~ above H & E staining is often valuable in the histological diagnosis that skin conditions like psoriasis, lichen planus, Bowen disease, and actinic keratosis amongst others.

The visibility of coarse KHG in cases of irritated seborrheic keratosis is beneficial to differentiate seborrheic keratosis native verruca vulgaris, as the rough circuit granules room a specific feature of irritated seborrheic keratosis.

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One of the key proteinaceous materials of KHG is filaggrin, which is necessary in facilitating to move compression and also the biogenesis of the stratum corneum.  Loss-of-function mutations involving the filaggrin gene has been displayed to be the cause of plenty of conditions, including monogenic genodermatosis ichthyosis vulgaris and also atopic dermatitis (eczema). A variety of independent and also complementary genetic studies show that inheritance that loss-of-function mutation in the filaggrin gene (FLG) confers a high threat of ad and associated atopic conditions like ichthyosis vulgaris.<10>